Tubulin Beta-3 Chain as a New Candidate Protein Biomarker of Human Skin Aging: A Preliminary Study.

Sylvia G Lehmann,Michel Seve,Sandrine Bourgoin-Voillard,Walid Rachidi

doi:10.1155/2017/5140360

Abstract

Skin aging is a complex process, and a lot of efforts have been made to identify new and specific targets that could help to diagnose, prevent, and treat skin aging. Several studies concerning skin aging have analyzed the changes in gene expression, and very few investigations have been performed at the protein level. Moreover, none of these proteomic studies has used a global quantitative labeled proteomic offgel approach that allows a more accurate description of aging phenotype. We applied such an approach on human primary keratinocytes obtained from sun-nonexposed skin biopsies of young and elderly women. A total of 517 unique proteins were identified, and 58 proteins were significantly differentially expressed with 40 that were downregulated and 18 upregulated with aging. Gene ontology and pathway analysis performed on these 58 putative biomarkers of skin aging evidenced that these dysregulated proteins were mostly involved in metabolism and cellular processes such as cell cycle and signaling pathways. Change of expression of tubulin beta-3 chain was confirmed by western blot on samples originated from several donors. Thus, this study suggested the tubulin beta-3 chain has a promising biomarker in skin aging.

Highlights

Life expectancy in developed countries over the past two centuries has considerably increased, and if this trend continues through the 21st century, most babies born since 2000 in such countries will reach 100 years
In order to obtain a quantitative proteomic map of elderly and young donor-derived keratinocyte cells, we used an iTRAQ labeling coupled with OFFGEL fractionation and off-line nanoLC/ MS/MS as previously described [24]
The bioinformatics analysis with Paragon and Mascot search engines resulted in the identification of 517 unique proteins using a 1% False Discovery Rate Analysis (FDR) and considering only proteins with at least 1 peptide with confidence level ≥ 95% and score > 30

Summary

Introduction

Life expectancy in developed countries over the past two centuries has considerably increased, and if this trend continues through the 21st century, most babies born since 2000 in such countries will reach 100 years. Aging is a complex process influenced by multiple genetic and environmental factors and is characterized by a progressive decline in multiple physiological functions. Skin like other organs is affected by aging that can be accelerated by environmental factors such as UV radiation. Thereby, skin is an interesting alternative approach to decipher the intrinsic aging process as it is accessible compared to internal organs or tissues. Skin undergoes several morphological and physiological changes with intrinsic aging such as fine wrinkle formation, thinning of the epidermis and dermis, increased vulnerability and fragility, dryness, loss of elasticity, and disturbed barrier function [2]. The underlying mechanisms of intrinsic aging are multiple: cellular senescence and decreased proliferative capacity; shortening of the telomeres; increase in DNA damage and reduction in DNA repair processes; mitochondrial and genomic DNA mutations; hormonal decline and oxidative stress [3, 4]

Objectives

Methods

Results

Discussion

Conclusion